This invention relates to graft devices and methods capable of promoting endogenous tissue restoration or growth.
There is long remaining need for off-the-shelf small diameter replacement vessels to overcome the drawbacks of currently available alternatives.
Coronary Artery Bypass Grafting (CABG) is the most common open heart surgical procedure and is performed more than a million times per year worldwide. In 80% of CABG procedures, native vein segments (2-3 on average per procedure) are used for coronary revascularization, thus requiring an additional painful surgical procedure to harvest the vein from the patient's leg, which is often associated with complications such as infections and chronic pain. Despite rigorous efforts, no synthetic off-the-shelf alternatives for this application exist today. Commonly used vascular prosthesis, such as those based on ePTFE or Dacron are not commercially available for CABG as these grafts fail to remain patent (open) in diameters of 4 mm and below as required for CABG.
Furthermore, in other small diameter vessel applications, such as dialysis access grafts or in peripheral applications such as Critical Limb Ischemia (CLI) there is still a large unmet medical need, despite the slightly larger diameters (typically 6, and up to 8 mm), both native veins and prosthetic grafts do not provide satisfactory long-term patency. The problem with prosthetic grafts in these applications is that they do not allow restoration of natural tissue, and therefore they cannot heal adequately. Eventually, these grafts occlude because deposited proteins and tissues from the blood stream accumulate within these grafts with time, eventually resulting in stenosis and occlusion.
Accordingly, there is a need in the art to provide a graft device for restoring a vessel by being capable of promoting endogenous tissue restoration or growth, while maintaining the structural and dynamical requirements desired for a graft device. The present invention provides a graft device that addresses this need.
The present invention provides a graft device for endogenous tissue restoration in between two tubular structures. In one embodiment, the graft device distinguishes an electrospun inner tubular layer, an electrospun outer tubular layer; and a graft support device defined as a zig-zag patterned helix having an inner tubular surface and an outer tubular surface. The electrospun inner tubular layer matches the inner tubular surface, and the electrospun outer tubular layer matches the outer tubular surface. Together the electrospun inner tubular layer and the electrospun outer tubular layer sandwich the graft support device. In one embodiment, the zig-zag patterned helix takes up about 95% of the length of the graft device.
The graft device is deployable in a predetermined state or wherein the graft device maintains a predetermined state upon implantation.
The graft support device further distinguishes first areas defined by the corners of the zig-zag pattern, and second areas defined by areas within each V or inverted-V within the zig-zag pattern minus the first area defined as their respective corners.
The first areas are non-laminated areas where the electrospun inner tubular layer and the electrospun outer tubular layer are not-laminated together. These first non-laminated areas enable bending of the graft support device, while preventing kinking of the graft support device. In one example, the first non-laminated area for each corner has a surface area in a range of 0.3 to 0.5 mm2.
The second areas are laminated areas where the electrospun inner tubular layer and the electrospun outer tubular layer are laminated together. In one example, the second laminated area for each within each V or inverted-V has a surface area in a range of 2.5 to 3.5 mm2.
In one embodiment, the graft support device is made out of a metal or a polymer, and the electrospun inner and outer tubular layer are made out of polymer fibers, and where the second areas have a polymer to helix metal or helix polymer circumferential surface area ratio ranging from 4:1 to 12:1 (8:1).
In yet a further embodiment, each corner within the graft support device is an n-like shape or a u-like shape depending on the direction within the zig-zag pattern and each corner has a surface area in a range of 0.3 to 0.5 mm2. The graft support device has a uniform pitch angle.
In yet a further embodiment, the electrospun inner and outer tubular layer are each porous biodegradable polymer layers with a porosity large enough to allow for cell ingrowth upon implantation to promote the endogenous tissue restoration or growth. The electrospun inner and outer tubular layer are replaced over time by the endogenous tissue restoration or growth as a result of the cell ingrowth.
In yet a further embodiment, the graft support device at one end or at both ends has one or more independent C-rings distributed and positioned at an acute orientation angle relative to a longitudinal axis of the graft device.
In yet a further embodiment, the graft support device at one end or at both ends have a closed ring connected to the graft support device.
In still another embodiment, the invention provides a graft device distinguishing an electrospun inner tubular layer, an electrospun outer tubular layer, and a graft support device defined as a patterned helix having an inner tubular surface and an outer tubular surface. Similarly, as the graft device described above, the electrospun inner tubular layer matches the inner tubular surface, the electrospun outer tubular layer matches the outer tubular surface, and together the electrospun inner tubular layer and the electrospun outer tubular layer sandwich the patterned helix distinguishing laminated areas and non-laminated areas. The non-laminated areas enable bending of the patterned helix, while preventing kinking of the graft support device.
In still another embodiment, the invention provides a method of creating a connection between two tubular structures using a graft device. Here the graft device distinguishes an electrospun inner tubular layer, an electrospun outer tubular layer, and a graft support device defined as a patterned helix having an inner tubular surface and an outer tubular surface. Similarly, as the graft devices described above, the electrospun inner tubular layer matches the inner tubular surface, the electrospun outer tubular layer matches the outer tubular surface, and together the electrospun inner tubular layer and the electrospun outer tubular layer sandwich the patterned helix distinguishing laminated areas and non-laminated areas. The non-laminated areas enable bending of the patterned helix, while preventing kinking of the graft support device. After implantation of the graft device, the electrospun inner and outer tubular layer are substantially replaced over time by the endogenous tissue restoration or growth as a result of the cell ingrowth.
Embodiments of this invention have the following advantages:
There is a need in the art to provide a graft device for restoring a vessel by being capable of promoting endogenous tissue restoration or growth, while maintaining the structural and dynamical requirements desired for a graft device. The present invention provides a graft device that addresses this need.
In one embodiment, the graft device is a tubular implant for making an anastomotic connection in between two tubular structures. Examples of tubular implants include, without limitation, a vein, an artery, a urethra, an intestine, an esophagus, a trachea, a bronchii, a ureter, or a fallopian tube. The graft device intended in this invention is not a device for endoluminal placement—i.e. inside the lumen of an existing tubular structure.
In one embodiment, the graft device 100 has an electrospun inner tubular layer 110 and an electrospun outer tubular layer 120 (
Embodiments of this invention are not limited to a graft support device from a zig-zag patterned helix as long as the patterned helix can achieve the goal of a graft device with laminated and non-laminated areas with the objectives for bending enablement and kinking prevention. The device has an electrospun inner and outer tubular layer with a patterned helix having an inner tubular surface and an outer tubular surface. The electrospun inner tubular layer matches the inner tubular surface, and the electrospun outer tubular layer matches the outer tubular surface. Together the electrospun inner tubular layer and the electrospun outer tubular layer sandwich the patterned helix distinguishing laminated areas and non-laminated areas. The non-laminated areas enable bending of the patterned helix, while preventing kinking of the zig-zag patterned helix.
Referring back to the example of the zig-zag patterned helix, this pattern distinguishes first areas 310 defined by the corners of the zig-zag pattern (
The zig-zag patterned helix distinguishes second areas 320 defined by areas within each V or inverted-V within the zig-zag pattern minus the first area defined as their respective corners (
The zig-zag patterned helix can be made out of a metal (e.g. nitinol) or a polymer, and the electrospun inner and outer tubular layer can be made out of polymer fibers. In one embodiment, electrospun polymer to metal (or polymer) circumferential/cylindrical surface area ratio ranges from 4:1 to 12:1 (defined for the graft device). In one exemplary embodiment this ratio is about 8:1. The circumferential/cylindrical surface area is measured on the outer surface of the graft supporting device.
It is important for the embodiments that the electrospun inner and outer tubular layer are each porous biodegradable polymer layers with a porosity large enough to allow for cell ingrowth upon implantation to promote the endogenous tissue restoration or growth. The electrospun inner and outer tubular layers are replaced over time by the endogenous tissue restoration or growth as a result of the cell (in)growth.
For the specific design of the graft support device in this invention each corner within the zig-zag patterned helix is an n-like shape 330 or a u-like shape 340 depending on the direction within the zig-zag pattern as shown in
The n-like shape or the u-like shape are narrow and as such do not allow electrospun inner and outer polymer fibers to adhere/bond locally to each other, i.e. remain delaminated. Rather these n-like shape or a u-like shapes serve as “hinge areas” where relative movement between the helix and the electrospun layers is possible due to relative high metal density and where local electrospun polymer fibers are not able to interconnect through the u-like or n-like shaped structures of the metal/polymer (i.e. first areas).
The zig-zag patterned helix can be made out of a laser cut tube. In some embodiments, connecting struts (“bridges”) 410 can be considered to improve manufacturing yield (
In one example, the uniform pitch angle 132 as shown in
The uniform pitch angle 132 as shown in
The graft manufacturing process starts by electrospinning of an inner layer on tubular mandrel. The inner layer is spun such that its outer diameter corresponds to the inner diameter of the graft support device, resulting in sufficient friction between the two components. The graft support device is then expanded and loaded on a tube. The tube inner diameter is larger than the spun inner layer outer diameter such that it serves as a deployment tool for the graft support device to be deployed in its desired location axially over the inner layer. The next step is to electrospin the outer layer, in a special process designed to reach optimal adherence (i.e. lamination) of the outer layer fibers to those of the inner layer at the non-metal covered areas. This process assures that the second areas are fully laminated and was tested and validated on benchtop. The aforementioned specifications of the support element (i.e. polymer to support element density, cell to cell spacing) were designed to result in optimal lamination of the fibers.
In a further embodiment shown in
C-rings are defined as either a circular or oval ring that is not fully closed; i.e. has an opening, large enough to accommodate standard surgical scissors for axial slit creation without cutting through the ring strut. In one embodiment, the openings of the C-rings are aligned with each other. In an alternate embodiment, the C-rings could be closed rings.
The C-rings are embedded in between the inner and outer tubular layers, in a way that prevents delamination of the layers. In one embodiment, the orientation angle is nominally about 45 degrees. In a preferred embodiment, the C-rings are made of nitinol.
In one embodiment, the patterned helix part of the graft support device 612 has an oval or circular end-ring 624 attached to (and part of) the patterned helix part. This so-called end-ring 624 is aligned more or less in parallel to the two or more independent C-rings. In a preferred embodiment, the end ring is made of nitinol.
Note is that this end-ring is physically connected to the graft support device. This ring is always fully closed. This is important as it prevents the graft from collapsing and stabilizes the end part of the graft. Furthermore, it makes the graft support device non-expandable and different from endoluminal devices such as stents.
The electrospun material referenced in this document may comprise the ureido-pyrimidinone (UPy) quadruple hydrogen-bonding motif (pioneered by Sijbesma (1997), Science 278, 1601-1604) and a polymer backbone, for example selected from the group of biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinylalcohol, polypropylenefumarate. Examples of polyesters are polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and their copolyesters. Examples of polycarbonates are poly(trimethylenecarbonate), poly(dimethyltrimethylenecarbonate), poly(hexamethylene carbonate).
The same result may be obtained with alternative, non-supramolecular polymers, if properties are carefully selected and material processed to ensure required surface characteristics. These polymers may comprise biodegradable or non-biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinylalcohol, polypropylenefumarate. Examples of polyesters are polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and their copolyesters. Examples of polycarbonates are poly(trimethylenecarbonate), poly(dimethyltrimethylenecarbonate), poly(hexamethylene carbonate).
Filing Document | Filing Date | Country | Kind |
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PCT/EP2021/081445 | 11/12/2021 | WO |
Number | Date | Country | |
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63113283 | Nov 2020 | US |